Abstract
Purpose :
Recently, gene augmentation therapy with voretigene neparvovec (Luxturna®) was approved for clinical use (USA 2017, Europe 2018, United Arab Emirates and Saudi Arabia 2019). Among the EVICR.net clinical sites, we conducted the first multinational survey to understand management and experience of IRD cases in Europe with a special focus on RPE65-associated IRDs.
Methods :
An electronic survey questionnaire including 29 questions specifically addressing RPE65-associated IRDs was developed and sent to the 101 EVICR.net clinical sites.
Results :
The overall response rate was 49% (range by country 22% to 73%). 42 centers see IRD patients, of which 22 follow patients with confirmed biallelic RPE65 mutations. Nation wise, 33% to 100% of the responding centers manage such patients. 15/22 centers (68%) and 3/22 (14%) follow 1-5 and 6-10 patients with homozygous RPE65 mutations, respectively. 15/22 (68%) and 3/22 (14%) follow 1-5 and >20 patients with compound heterozygous RPE65 mutations, respectively. 65% of mutations were ACMG Class 4 and 5 (at least one allele), 68% reported previously and 14% novel. Referral diagnoses (mean per center) were Leber Congenital Amaurosis (34.8%), Early-onset severe retinal degeneration (15.3%), Rod-Cone-Dystrophy/Retinitis pigmentosa (25.6%), and unclassified visual impairment (15.9%). 25% of the centers changed the referral diagnosis in > 40% of cases; 32% follow a specific referral process for RPE65-associated IRD patients. Yearly follow-up visits are done in 55% of the centers, and biannual visits in 23%. In 32%, other centers also follow the patients. Kinetic perimetry is done in 82%, static perimetry in 45%, microperimetry in 18%. Fullfield Light Stimulus Threshold Testing (FST) with blue and red stimuli to quantify rod and cone function is used in 6/22 centers (27%). A mobility parcours is available in one center (5%).
Conclusions :
This first multinational survey on management of patients with RPE65 associated IRDs in Europe shows that about half of the responding EVICR.net centers have such patients under care. There is heterogeneity in diagnoses and management practices. At the start of clinical practice experience with voretigene neparvovec, these data provide a useful baseline and highlight the need for consensus/guidelines to inform standard of care in this new era of gene therapy.
This is a 2020 ARVO Annual Meeting abstract.